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1“Diagnostic value of procalcitonin in well appearing young febrile infants”Pediatrics 2012; 130:

2BackgroundWell appearing babies who are febrile are a diagnostic challenge.Current practise in the UK and SCH is to use WCC and CRP to aid diagnosis of invasive bacterial infection – but value as diagnostic markers variable.Procalcitonin increasingly used across Europe for the management of febrile babies and other bacterial infections.

3Procalcitonin (PCT) Peptide precursor of the hormone calcitonin.Produced by parafollicular cells of the Thyroid, lungs and intestines.Levels rapidly rise in response to bacterial infection, not with viral infection.½ life 25-30hrs

16Was there a clear question for the study to address?YesIn babies under 3 months who are febrile and appear well, do PCT levels offer good prognostic value to identify invasive bacterial infection?

17Was there a comparison with an appropriate reference standard?YesComparison to CRP, WCC and TNC

18Did all the patients get the diagnostic test and the reference standard?But 99.8% did get both PCT and CRP, so nearly!

19Could the results of the test of interest have been influenced by the results of the reference standard?NoBoth CRP and PCT measured in 99.8% of cases

20Is the disease status of the of the tested population clearly described?YesInvasive bacterial infection confirmed on blood culture or positive CSF

21Were the methods for performing the test described in sufficient detail?Yes, but….Explained in detail but some discrepancies:Some centres used “normal paediatric assessment triangle”, some didn’t.Variation in collection of urine(Spain SPA or catheter, Italy bag urine x2)Therefore different rates of “UTI” (22 vs 30%)

25Are the results presented in such a way we can work them out?NoOne small table of actual figures, all other results are statistical diagrams and calculated figures.Ranges of figures don’t match the text.

26Are the results presented in such a way we can work them out?No, ctdDifferent graphs and cut-off points mentioned at different times.Only 23 IBIs, could have shown values for each

27“Only PCT ≥0.5ng/mL was found to be an independent risk factor for IBI in the multivariate analysis (odds ratio 21.69)”?

29How sure are we about the results?Not so sure?Receiver operator curve areas, CIs all overlapMany false +ves and –vesText and tables don’t matchUnreliable and inconsistent urine collection? No meningitis in all patients

30Can the results be applied to the patients of Sheffield?Yes/NoDeveloped populations, similar diagnostic criteria and similar disease processesBut what cutoff points would we use?SBI not reliable, and we rarely use urine bags and catheters for samples. Also, don’t use urine dip < 1 year.Better performance when ruling in an infection, more useful clinicallyOnly 2% of these patients had IBI, and results didn’t mention if these were the patients who became clinically unwell anyway, or at what time (not excluded)

32Were all outcomes important to the individual or population considered?YesEarly detection of IBI and prompt use of antibiotics would improve outcome

33What would be the impact of using this test on the patients in Sheffield?? More IBI diagnosed early and treated promptly, leading to better outcome? Less antibiotics prescribed for non IBIs.Additional benefit, or instead of CRP?

34ConclusionPositivesGood idea and potentially a good pro-inflammatory marker.Seems to perform well, with good +ve LR.Positive predictor more useful, to identify the 2% with IBI and start abxBetter than CRP, but is this good enough to change practise?